tbuckley/cabot-search huggingface dataset:
The comparison of efficacy and safety evaluation of vacuum-assisted Elite 10-G system and the traditional BARD 14-G core needle in breast diagnosis: an open-label, parallel, randomized controlled trial
Authors: Ying Zhang, Junjie Li, Miao Mo, Juping Shen, Hui Ren, Shiping Li, Guangyu Liu, Zhimin Shao
Journal: International Journal of Surgery (2023)

Vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) are both widely used methods in diagnosing breast lesions. We aimed to determine whether the Elite 10-gauge VAB achieves higher accuracy than the BARD spring-actuated 14-gauge CNB.This was a phase 3, open-label, parallel, randomized controlled trial (NCT04612439). In total, 1470 patients with ultrasound (US)-visible breast lesions requiring breast biopsy were enrolled from April to July 2021 and randomized at a 1 : 1 ratio to undergo VAB or CNB. All patients underwent surgical excision after needle biopsy. The primary outcome was accuracy, defined as the proportion of patients who had a consistent qualitative diagnosis between the biopsy and surgical pathology results. The underestimation rate, false-negative rate and safety evaluations were the secondary endpoints.A total of 730 and 732 patients were evaluable for endpoints in the VAB and CNB groups, respectively. The accuracy of VAB surpassed that of CNB in the whole population (94.8 vs. 91.1%, P =0.009). The overall malignant underestimation rate was significantly lower in the VAB group than in the CNB group (21.4 vs. 30.9%, P =0.035). Additionally, significantly more false-negative events were noted in the CNB group (4.9 vs. 7.8%, P =0.037). In patients who presented with accompanying calcification, the accuracy of VAB surpassed that of CNB (93.2 vs. 88.3%, P =0.022). The potential superiority of VAB was indicated in patients with heterogeneous echo on US.In general, the 10-G VAB procedure is a reasonable alternative to the 14-G CNB procedure with higher accuracy. We recommend the use of VAB for lesions with accompanying calcification or heterogeneous echo on US.
Pink, Dome-Shaped Papule of the Scalp in a Patient With Multiple Squamous Cell Carcinomas
Authors: Yen Luu, Edward William Seger, Ting Wang
Journal: JAMA Dermatology (2023)

A 74-year-old man with a history of multiple squamous cell carcinomas presents with a 5-mm bright pink, dome-shaped papule with overlying vessels at the crown of the scalp. What is your diagnosis?
RSV Vaccine, Monoclonal Antibody Safe, Effective in Phase 3 Trials
Authors: Emily Harris
Journal: JAMA (2023)

Urine Tests May Miss More Than 400 000 STIs in the US Every Year Using vaginal swabs to test for sexually transmitted infections (STIs) picked up significantly more cases of Chlamydia trachomatis and Neisseria gonorrhoeae than using urine tests, according to a metaanalysis of 28 studies conducted from 1995 through 2021.Vaginal swabs were also more sensitive for Trichomonas vaginalis, although the difference between test types was not significant.Despite guidelines released in 2014 by the US Centers for Disease Control and Prevention in favor of vaginal swabs, most samples analyzed by public health laboratories continue to be urine.The researchers estimated that depending on urine rather than vaginal swab testing could result in more than 400 000 missed STI cases each year."[V]aginal sampling should be the initial choice offered to patients," the researchers wrote in the Annals of Family Medicine, with urine samples only collected from those for whom a vaginal sample is unacceptable.Implementation research is needed to change physicians' go-to tests, they noted.
Large-scale phage cultivation for commensal human gut bacteria
Authors: Juntao Shen, Jieqiong Zhang, Luofei Mo, Yanchen Li, Yake Li, Cun Li, Xiaoxian Kuang, Zining Tao, Zepeng Qu, Lu Wu, Junyu Chen, Shiying Liu, Linfang Zeng, Zexi He, Zuohong Chen, Yu Deng, Tong Zhang, Bing Li, Lei Dai, Yingfei Ma
Journal: Cell Host & Microbe (2023)
Networking between helminths, microbes, and mammals
Authors: P’ng Loke, Nicola L. Harris
Journal: Cell Host & Microbe (2023)

Just as mammals have coevolved with the intestinal bacterial communities that are part of the microbiota, intestinal helminths represent an important selective force on their mammalian host. The complex interaction between helminths, microbes, and their mammalian host is likely an important determinant of mutual fitness. The host immune system in particular is a critical interface with both helminths and the microbiota, and this crosstalk often determines the balance between tolerance and resistance against these widespread parasites. Hence, there are many examples of how both helminths and the microbiota can influence tissue homeostasis and homeostatic immunity. Understanding these processes at a cellular and molecular level is an exciting area of research that we seek to highlight in this review and that will potentially guide future treatment approaches.
Assembling symbiotic bacterial species into live therapeutic consortia that reconstitute microbiome functions
Authors: Rita A Oliveira, Eric G Pamer
Journal: Cell Host & Microbe (2023)

Increasing experimental evidence suggests that administering live commensal bacterial species can optimize microbiome composition and lead to reduced disease severity and enhanced health. Our understanding of the intestinal microbiome and its functions has increased over the past two decades largely due to deep sequence analyses of fecal nucleic acids, metabolomic and proteomic assays to measure nutrient use and metabolite production, and extensive studies on the metabolism and ecological interactions of a wide range of commensal bacterial species inhabiting the intestine. Herein, we review new and important findings that have emerged from this work and provide thoughts and considerations on approaches to re-establish and optimize microbiome functions by assembling and administering commensal bacterial consortia.
Not all exons are protein coding: Addressing a common misconception
Authors: Julie L. Aspden, Edward W.J. Wallace, Nicola Whiffin
Journal: Cell Genomics (2023)

Exons are regions of DNA that are transcribed to RNA and retained after introns are spliced out. However, the term "exon" is often misused as synonymous to "protein coding," including in some literature and textbook definitions. In contrast, only a fraction of exonic sequences are protein coding (<30% in humans). Both exons and introns are also present in untranslated regions (UTRs) and non-coding RNAs. Misuse of the term exon is problematic, for example, "whole-exome sequencing" technology targets <25% of the human exome, primarily regions that are protein coding. Here, we argue for the importance of the original definition of an exon for making functional distinctions in genetics and genomics. Further, we recommend the use of clearer language referring to coding exonic regions and non-coding exonic regions. We propose the use of coding exome sequencing, or CES, to more appropriately describe sequencing approaches that target primarily protein-coding regions rather than all transcribed regions.
On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis
Authors: Felix M. Key, Veda D. Khadka, Carolina Romo-González, Kimbria J. Blake, Liwen Deng, Tucker C. Lynn, Jean C. Lee, Isaac M. Chiu, Maria T. García-Romero, Tami D. Lieberman
Journal: Cell Host & Microbe (2023)

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.
Prevalence, Progression, and Modifiable Risk Factors for Diabetic Retinopathy in Youth and Young Adults With Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study
Authors: Elizabeth T. Jensen, Joseph Rigdon, Kasra A. Rezaei, Jinan Saaddine, Elizabeth A. Lundeen, Dana Dabelea, Lawrence M. Dolan, Ralph D’Agostino, Barbara Klein, Stacy Meuer, Matthew T. Mefford, Kristi Reynolds, Santica M. Marcovina, Amy Mottl, Beth Mayer-Davis, Jean M. Lawrence
Journal: Diabetes Care (2023)

To determine the prevalence, progression, and modifiable risk factors associated with the development of diabetic retinopathy (DR) in a population-based cohort of youth-onset diabetes.
Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland
Authors: Caroline F. Wright, Patrick Campbell, Ruth Y. Eberhardt, Stuart Aitken, Daniel Perrett, Simon Brent, Petr Danecek, Eugene J. Gardner, V. Kartik Chundru, Sarah J. Lindsay, Katrina Andrews, Juliet Hampstead, Joanna Kaplanis, Kaitlin E. Samocha, Anna Middleton, Julia Foreman, Rachel J. Hobson, Michael J. Parker, Hilary C. Martin, David R. FitzPatrick, Matthew E. Hurles, Helen V. Firth
Journal: New England Journal of Medicine (2023)

Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits.
High Prevalence of NASH and Advanced Fibrosis in Type 2 Diabetes: A Prospective Study of 330 Outpatients Undergoing Liver Biopsies for Elevated ALT, Using a Low Threshold
Authors: Laurent Castera, Cédric Laouenan, Anaïs Vallet-Pichard, Tiphaine Vidal-Trécan, Pauline Manchon, Valérie Paradis, Dominique Roulot, Nathalie Gault, Christian Boitard, Benoit Terris, Hélène Bihan, Jean-Baptiste Julla, Alina Radu, Thierry Poynard, Angélique Brzustowsky, Etienne Larger, Sébastien Czernichow, Stanislas Pol, Pierre Bedossa, Dominique Valla, Jean-François Gautier, Christophe Junot, Bernard Van Beers, Christian Boitard, Nathalie de Préville, Isabelle Durand Zaleski, Pierre-Emmanuel Rautou, Marco Dioguardi, Valérie Vilgrain, Jean-Pierre Riveline
Journal: Diabetes Care (2023)

OBJECTIVE Most people with type 2 diabetes (T2DM) and nonalcoholic steatohepatitis (NASH) or advanced fibrosis (AF) remain undiagnosed, resulting in missed opportunities for early intervention. This multicenter, prospective study assessed the yield of using routinely available data to identify these patients. RESEARCH DESIGN AND METHODS A total of 713 outpatients with T2DM, screened in four diabetology clinics for nonalcoholic fatty liver disease according to American Diabetes Association criteria, were referred to hepatologists for further work-up (Fibrosis-4 and vibration-controlled transient elastography [VCTE]). A liver biopsy was proposed when ALT levels were persistently &amp;gt;20 IU/L in female patients or &amp;gt;30 IU/L in male patients, in the absence of other liver disease. RESULTS Liver biopsies were performed in 360 patients and considered adequate for reading after central review for 330 specimens (median patient age, 59 years; male patients, 63%; median BMI and HbA1c values, 32 and 7.5%, respectively). Prevalence of NASH, AF, and cirrhosis were 58%, 38%, and 10%, respectively. Liver lesions were independently associated with the components of metabolic syndrome but not with the micro- and macrovascular complications of T2DM. Models based on routinely available data with or without VCTE had good accuracy to predict AF (respectively: area under the receiver operating characteristic curve [AUROC], 0.84 and 0.77; and correctly classified 59% and 45%) and NASH (respectively: AUROC, 0.82 and 0.81; 44% and 42%). CONCLUSIONS Despite the use of a low ALT threshold, prevalence of NASH (58%) or AF (38%) was high. Routinely available data had a high yield in identifying patients with T2DM with AF and/or NASH requiring further liver assessment.
Gestational Diabetes Mellitus, Postpartum Lipidomic Signatures, and Subsequent Risk of Type 2 Diabetes: A Lipidome-Wide Association Study
Authors: Guoying Wang, Jessie P. Buckley, Tami R. Bartell, Xiumei Hong, Colleen Pearson, Xiaobin Wang
Journal: Diabetes Care (2023)

To identify a postpartum lipidomic signature associated with gestational diabetes mellitus (GDM) and investigate the role of the identified lipids in the progression to type 2 diabetes (T2D).
Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery
Authors: Luis D. Pacheco, Rebecca G. Clifton, George R. Saade, Steven J. Weiner, Samuel Parry, John M. Thorp, Monica Longo, Ashley Salazar, Wendy Dalton, Alan T.N. Tita, Cynthia Gyamfi-Bannerman, Suneet P. Chauhan, Torri D. Metz, Kara Rood, Dwight J. Rouse, Jennifer L. Bailit, William A. Grobman, Hyagriv N. Simhan, George A. Macones
Journal: New England Journal of Medicine (2023)

Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. Download a PDF of the Research Summary. We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P=0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was −1.8 g per deciliter and −1.9 g per deciliter, respectively (mean difference, −0.1 g per deciliter; 95% CI, −0.2 to −0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.) QUICK TAKE VIDEO SUMMARYTranexamic Acid after Cesarean Delivery 01:35
Dersimelagon in Erythropoietic Protoporphyrias
Authors: Manisha Balwani, Herbert L. Bonkovsky, Cynthia Levy, Karl E. Anderson, D. Montgomery Bissell, Charles Parker, Fumihiro Takahashi, Robert J. Desnick, Kirstine Belongie
Journal: New England Journal of Medicine (2023)

Erythropoietic protoporphyria and X-linked protoporphyria are inborn errors of heme biosynthesis that cause elevated circulating levels of metal-free protoporphyrin and phototoxicity. Both disorders are characterized by excruciating phototoxic attacks after exposure to visible light. Dersimelagon is a new, orally administered, selective melanocortin 1 receptor agonist that increases levels of skin eumelanin. Download a PDF of the Research Summary. We conducted a randomized, placebo-controlled, phase 2 trial to investigate the efficacy and safety of dersimelagon with respect to the time to onset and the severity of symptoms associated with sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria. Patients 18 to 75 years of age were randomly assigned in a 1:1:1 ratio to receive placebo or dersimelagon at a dose of 100 or 300 mg once daily for 16 weeks. The primary end point was the change from baseline to week 16 in the time to the first prodromal symptom associated with sunlight exposure. Patients recorded daily sunlight exposure and symptom data in an electronic diary. Quality of life and safety were also assessed. Of the 102 patients (93 with erythropoietic protoporphyria and 9 with X-linked protoporphyria) who underwent randomization, 90% completed the treatment period. The mean daily time to the first prodromal symptom associated with sunlight exposure increased significantly with dersimelagon: the least-squares mean difference from placebo in the change from baseline to week 16 was 53.8 minutes in the 100-mg dersimelagon group (P=0.008) and 62.5 minutes in the 300-mg dersimelagon group (P=0.003). The results also suggest that quality of life improved in patients receiving dersimelagon as compared with placebo. The most common adverse events that occurred or worsened during treatment were nausea, freckles, headache, and skin hyperpigmentation. At both doses evaluated, dersimelagon significantly increased the duration of symptom-free sunlight exposure in patients with erythropoietic protoporphyria or X-linked protoporphyria. (Funded by Mitsubishi Tanabe Pharma; Endeavor ClinicalTrials.gov number, NCT03520036.) QUICK TAKE VIDEO SUMMARYDersimelagon for Erythropoietic Protoporphyrias 02:01
Effect of Donor Sex on Recipient Mortality in Transfusion
Authors: Michaël Chassé, Dean A. Fergusson, Alan Tinmouth, Jason P. Acker, Iris Perelman, Angie Tuttle, Shane W. English, Steven Hawken, Alan J. Forster, Nadine Shehata, Kednapa Thavorn, Kumanan Wilson, Nancy Cober, Heather Maddison, Melanie Tokessy
Journal: New England Journal of Medicine (2023)

Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited.In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group.A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06).This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).
HIV establishes an early foothold
Authors: Jose A. Moran, Matthew D. Marsden
Journal: Cell Host & Microbe (2023)

The weeks following HIV acquisition are a critical time when the virus causes significant immunological damage and establishes long-term latent reservoirs. A recent study in Immunity by Gantner et al. uses single-cell analysis to explore these key early infection events, providing insights into early HIV pathogenesis and reservoir formation. The weeks following HIV acquisition are a critical time when the virus causes significant immunological damage and establishes long-term latent reservoirs. A recent study in Immunity by Gantner et al. uses single-cell analysis to explore these key early infection events, providing insights into early HIV pathogenesis and reservoir formation. HIV rapidly targets a diverse pool of CD4+ T cells to establish productive and latent infectionsGantner et al.ImmunityFebruary 17, 2023In BriefThe early cellular targets of HIV and the mechanisms of viral dissemination in humans remain elusive. Gantner et al. demonstrate that the early targets of HIV rapidly change during acute infection and differ between blood and lymph nodes. They also observe that latent and genetically intact proviruses persisting during therapy are archived from the earliest stages of acute infection. Full-Text PDF
Evaluation of a Fourth-Generation Subcutaneous Real-Time Continuous Glucose Monitor (CGM) in Individuals With Diabetes on Peritoneal Dialysis
Authors: Jack K.C. Ng, James Ling, Andrea O.Y. Luk, Eric S.H. Lau, Ronald C.W. Ma, Philip K.T. Li, Cheuk Chun Szeto, Juliana C.N. Chan, Elaine Chow
Journal: Diabetes Care (2023)

To evaluate the performance of a real-time continuous glucose monitor (CGM) in individuals with diabetes on peritoneal dialysis (PD).Thirty participants with type 2 diabetes on continuous ambulatory PD wore a Guardian Sensor 3 on the upper arm paired with Guardian Connect for 14 days. We compared CGM readings against Yellow Springs Instrument (YSI) venous glucose during an 8-h in-clinic session with glucose challenge.The mean absolute relative difference (MARD) was 10.4% (95% CI 9.6, 11.7) from 941 CGM-YSI matched pairs; 81.3% of readings were within %15/15 of YSI values in the full glycemic range. Consensus error grid analysis showed 99.9% of sensor values in zones A and B. There were no correlations between pH, uremia, hydration status, and MARD.We showed satisfactory performance of a real-time CGM sensor in PD patients with diabetes, supporting future use to facilitate treatment decisions.
Genomics in Clinical Practice
Authors: Jennifer E. Posey, James R. Lupski
Journal: New England Journal of Medicine (2023)

In a remarkable study notable for its scale (>13,500 families of probands), scope (all branches of pediatric clinical practice), and implementation in clinical practice, the Deciphering Developmental Disorders (DDD) project, led by Wright and colleagues,1 investigated rare genomic disease in the United Kingdom and Ireland. These investigators identified and communicated molecular diagnoses to thousands of families with members who had previously undiagnosed developmental disorders. The findings from this study show how a genome-driven approach in combination with detailed clinical phenotyping improves diagnostic yield over that with the previous standard of care. A multiple logistic-regression analysis of clinical and demographic information . . .